机构：[1]Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany.[2]Department of Ophthalmology, PLA Army General Hospital, Beijing, China.[3]Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway.[4]Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany.[5]Core Unit Peptide Technologies, Medical Faculty, Leipzig University, Leipzig, Germany.[6]Department of Ophthalmology, University Hospital, Inselspital, Bern, Switzerland.
The purpose of this study was to examine possible involvement of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1/Flt-1 in pigment epithelium-derived factor (PEDF)-promoted survival of retinal neurons.Survival of growth factor-deprived retinal ganglion cells (RGCs) and R28 cells and activation of ERK-1/-2 MAP kinases were assessed in the presence of PEDF, placental growth factor (PlGF), and VEGF using cell cultures, viability assays and quantitation of ERK-1/-2 phosphorylation. VEGFR-1/Flt-1 expression was determined using quantitative PCR (qPCR) and Western blotting. VEGFR-1/Flt-1 was knocked down in R28 cells by small interfering RNA (siRNA). Binding of a PEDF-IgG Fc fusion protein (PEDF-Fc) to retinal neurons, immobilized VEGFR-1/Flt-1 and VEGFR-1/Flt-1-derived peptides was studied using binding assays and peptide scanning.PEDF in combination with PlGF stimulated increased cell survival and ERK-1/-2 MAP kinase activation compared to effects of either factor alone. VEGFR-1/Flt-1 expression in RGCs and R28 cells was significantly upregulated by hypoxia, VEGF, and PEDF. VEGFR-1/Flt-1 ligands (VEGF and PlGF) or soluble VEGFR-1 (sflt-1) competed with PEDF-Fc for binding to R28 cells. Depleting R28 cells of VEGFR-1/Flt-1 resulted in reduced PEDF-Fc binding when comparing VEGFR-1/Flt-1 siRNA- and control siRNA-treated cells. PEDF-Fc interacted with immobilized sflt-1, which was specifically blocked by VEGF and PlGF. PEDF-Fc binding sites were mapped to VEGFR-1/Flt-1 extracellular domains D3 and D4. Peptides corresponding to D3 and D4 specifically inhibited PEDF-Fc binding to R28 cells. These peptides and sflt-1 significantly inhibited PEDF-promoted survival of R28 cells.These results suggest that PEDF can target VEGFR-1/Flt-1 and this interaction plays a significant role in PEDF-mediated neuroprotection in the retina.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|2 区医学
小类|2 区眼科学
最新[2023]版：
大类|2 区医学
小类|2 区眼科学
第一作者：
第一作者机构：[1]Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany.
通讯作者：
通讯机构：[1]Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany.[*1]University of Leipzig, Eye Hospital, Liebigstrasse 10-14, Leipzig D-04103, Germany
推荐引用方式(GB/T 7714)：
Meng Jie,Yang Xiu Mei,Scheer Oliver,et al.Pigment Epithelium-Derived Factor Binding to VEGFR-1 (Flt-1) Increases the Survival of Retinal Neurons[J].Investigative Ophthalmology & Visual Science.2024,65(10):27.doi:10.1167/iovs.65.10.27.
APA：
Meng Jie,Yang Xiu Mei,Scheer Oliver,Lange Johannes,Heidi Müller...&Eichler Wolfram.(2024).Pigment Epithelium-Derived Factor Binding to VEGFR-1 (Flt-1) Increases the Survival of Retinal Neurons.Investigative Ophthalmology & Visual Science,65,(10)
MLA：
Meng Jie,et al."Pigment Epithelium-Derived Factor Binding to VEGFR-1 (Flt-1) Increases the Survival of Retinal Neurons".Investigative Ophthalmology & Visual Science 65..10(2024):27
